The simian type D retroviruses are the cause of Simian Acquired Immunodeficiency Syndrome in biomedical research communities in Asian macaques, and can serve as model systems in understanding the role of envelope (env) glycoprotein gene diversity in modulating cell tropism and onset in AIDS pathogenesis. Retroviruses undergo high-frequency mutations in their env genes and are subjected to selection pressures that result in the appearance of new pathologically-advantaged variants. We have molecularly-cloned and sequenced the env genes and 3' long terminal repeat regions (LTRs) of a type D simian retrovirus (SRV serogroup 2; D2/RHE/OR) and variant viruses recovered from rhesus macaques endemically infected with the prototypical serogroup 2 virus. The prototypical virus induces mild transient immunosuppression in rhesus macaques and retains limited immune B cell tropism. The two variant viruses were recovered from rhesus macaques which developed severe immunodeficiency and possess expanded immune cell tropism and altered glycoprotein structure and immunoreactivity. Infectious molecular genomes of D2/RHE/OR and one variant, D2/RHE/OR/V1, have been recovered. Like the molecularly-cloned serogroup 2 SRV (D2/CEL/OR) isolated from Celebes macaque, the env genes from the rhesus-derived simian retroviruses encode a glycoprotein of 574 amino acids. The env genes of D2/RHE/OR and D2/CEL/OR are 96% similar at the amino acid level; the degree of similarity between the D2/RHE/OR and V1 glycoproteins is 98% (or 5 residue conversions). In addition, we have isolated infectious molecular clones of serogroup 5 SRV (D5/RHE/OR), and full-length molecular clones of serogroup 4 SRV (D4/CYN/CA). Sequence analyses of these additional genomic clones indicate that serogroups 4 and 5 SRVs are genetically-distinct from all previously characterized serogroups. The complete sequence analyses of the serogroup 4 and 5 SRVs will provide important information concerning the genetic diversity of the simian retroviruses, and will provide the necessary molecular reagents for future structure-function and cell/tissue tropism experiments.